Efficacy and Safety of Oral BG00012 in Relapsing-Remitting Multiple Sclerosis
DEFINE
A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
1 other identifier
interventional
1,234
28 countries
155
Brief Summary
To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. To determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions commonly seen in MS patients and slow down the time it takes for the disease to get worse. The purpose of this study is also to determine the safety of BG00012 and how well it is tolerated. Another goal is to see what effect BG00012 may have on tests and evaluations used to assess MS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2007
Typical duration for phase_3
155 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2007
CompletedFirst Submitted
Initial submission to the registry
January 8, 2007
CompletedFirst Posted
Study publicly available on registry
January 11, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2011
CompletedResults Posted
Study results publicly available
June 2, 2014
CompletedJanuary 26, 2015
January 1, 2015
4.1 years
January 8, 2007
May 5, 2014
January 13, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of Subjects Relapsed
A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurolgic evaluation committee. The proportion of subjects with a relapse was estimated using the Kaplan-Meier method, which was based on the time-to-first-relapse survival distribution.
2 years
Secondary Outcomes (5)
Number of New or Newly Enlarging T2 Hyperintense Lesions
2 years
Number of Gadolinium-enhancing T1-weighted Lesions
2 years
Number of Subjects With Gadolinium (Gd)-Enhancing Lesions
2 years
Annualized Relapse Rate
2 years
Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
2 years
Study Arms (3)
Placebo
PLACEBO COMPARATORParticipants received two placebo capsules orally three times daily (TID)
BG00012 240 mg Twice Daily (BID)
EXPERIMENTALParticipants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
BG00012 240 mg 3 Times Daily (TID)
EXPERIMENTALParticipants received two 120 mg BG00012 capsules orally three times daily (TID)
Interventions
Eligibility Criteria
You may qualify if:
- Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:
- Must have a confirmed diagnosis of RRMS according to McDonald criteria #1-4.
- Must have a baseline EDSS between 0.0 and 5.0, inclusive.
- Must have relapsing-remitting disease course.
You may not qualify if:
- Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease.
- Pregnant or nursing women.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (159)
Research Site
Gilbert, Arizona, United States
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Phoenix, Arizona, United States
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San Francisco, California, United States
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New Haven, Connecticut, United States
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Washington D.C., District of Columbia, United States
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Vero Beach, Florida, United States
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Atlanta, Georgia, United States
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Evanston, Illinois, United States
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Palos Heights, Illinois, United States
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Fort Wayne, Indiana, United States
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Indianapolis, Indiana, United States
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Des Moines, Iowa, United States
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Wichita, Kansas, United States
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Lexington, Kentucky, United States
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Brighton, Massachusetts, United States
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Hopedale, Massachusetts, United States
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Lexington, Massachusetts, United States
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Springfield, Massachusetts, United States
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Worcester, Massachusetts, United States
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Farmington Hills, Michigan, United States
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Minneapolis, Minnesota, United States
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Columbia, Missouri, United States
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St Louis, Missouri, United States
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Henderson, Nevada, United States
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Las Vegas, Nevada, United States
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Lebanon, New Hampshire, United States
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Albany, New York, United States
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Staten Island, New York, United States
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Raleigh, North Carolina, United States
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Dayton, Ohio, United States
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Erie, Pennsylvania, United States
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Hershey, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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East Providence, Rhode Island, United States
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Providence, Rhode Island, United States
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San Antonio, Texas, United States
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Newport News, Virginia, United States
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Wien, Virginia, United States
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Seattle, Washington, United States
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Camperdown, New South Wales, Australia
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Chatswood, New South Wales, Australia
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Fitzroy, Australia
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Geelong, Australia
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Heidelberg, Australia
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Kogarah, Australia
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Liverpool, Australia
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Melbourne, Australia
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Newcastle, Australia
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Vienna, Vienna, Austria
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Graz, Austria
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Innsbruck, Austria
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Linz, Austria
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Antwerp, Belgium
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Bruges, Belgium
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Charleroi, Belgium
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Diepenbeek, Belgium
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Leuven, Belgium
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Lommel, Belgium
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Sijsele-Damme, Belgium
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Woluwe, Belgium
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Banja Luka, Republic of Srpksa, Bosnia and Herzegovina
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Burnaby, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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Ottawa, Ontario, Canada
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LĂ©vis, Quebec, Canada
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Québec, Quebec, Canada
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Regina, Saskatchewan, Canada
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Montreal, Canada
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Zagreb, Croatia
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Brno, Czechia
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Jihlava, Czechia
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Opava, Czechia
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Ostrava, Czechia
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Pilsen, Czechia
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Prague, Czechia
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Teplice, Czechia
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Clermont-Ferrand, France
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Nice, France
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Paris, France
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Rennes, France
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Bad Neustadt-Saale, Germany
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Berlin, Germany
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Bochum, Germany
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DĂ¼sseldorf, Germany
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Essen, Germany
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Gieben, Germany
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Halle, Germany
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Hamburg, Germany
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Hanover, Germany
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Leipzig, Germany
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Minden, Germany
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MĂ¼nchen, Germany
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MĂ¼nster, Germany
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OsnabrĂ¼ck, Germany
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Westerstede, Germany
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Athens, Greece
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Ioannina, Greece
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Thessaloniki, Greece
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Guatemala City, Guatemala
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Chenna, India
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Coimbatore, India
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Delhi, India
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Hyderabad, India
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Kolkata, India
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Lucknow, India
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Mangalore, India
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Mumbai, India
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New Delhi, India
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Pune, India
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Ashkelon, Israel
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Beer Yaakov, Israel
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Jerusalem, Israel
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Tel Litwinsky, Israel
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Roma, Italy
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Guadalajara, Mexico
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Mexico City, Mexico
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San Luis PotosĂ City, Mexico
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Chisinau, Moldova
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Breda, Netherlands
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Sittard, Netherlands
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Christchurch, New Zealand
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Grafton, New Zealand
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Hamilton, New Zealand
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Skopje, North Macedonia
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Bialystok, Poland
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Gdansk, Poland
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Katowice, Poland
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Krakow, Poland
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Poznan, Poland
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Szczecin, Poland
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Warsaw, Poland
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Bucharest, Romania
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Cluj-Napoca, Romania
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Timișoara, Romania
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Belgrade, Serbia
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Kragujevac, Serbia
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Niš, Serbia
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Novi Sad, Serbia
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Bratislava, Slovakia
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Košice, Slovakia
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Martin, Slovakia
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Cape Town, South Africa
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Durban, South Africa
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Rosebank, South Africa
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Basel, Switzerland
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Sankt Gallen, Switzerland
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Zurich, Switzerland
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Lviv, Ukraine
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Odesa, Ukraine
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Poltava, Ukraine
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Zaporizhzhya, Ukraine
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London, United Kingdom
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Newcastle, United Kingdom
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Oxford, United Kingdom
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Sheffield, United Kingdom
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Staffordshire, United Kingdom
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Vienna, Virgin Islands
Related Publications (11)
Gold R, Arnold DL, Bar-Or A, Fox RJ, Kappos L, Chen C, Parks B, Miller C. Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years' follow-up of DEFINE, CONFIRM, and ENDORSE. Ther Adv Neurol Disord. 2020 May 12;13:1756286420915005. doi: 10.1177/1756286420915005. eCollection 2020.
PMID: 32426039DERIVEDMehta D, Miller C, Arnold DL, Bame E, Bar-Or A, Gold R, Hanna J, Kappos L, Liu S, Matta A, Phillips JT, Robertson D, von Hehn CA, Campbell J, Spach K, Yang L, Fox RJ. Effect of dimethyl fumarate on lymphocytes in RRMS: Implications for clinical practice. Neurology. 2019 Apr 9;92(15):e1724-e1738. doi: 10.1212/WNL.0000000000007262. Epub 2019 Mar 27.
PMID: 30918100DERIVEDFox RJ, Gold R, Phillips JT, Okwuokenye M, Zhang A, Marantz JL. Efficacy and Tolerability of Delayed-release Dimethyl Fumarate in Black, Hispanic, and Asian Patients with Relapsing-Remitting Multiple Sclerosis: Post Hoc Integrated Analysis of DEFINE and CONFIRM. Neurol Ther. 2017 Dec;6(2):175-187. doi: 10.1007/s40120-017-0077-5. Epub 2017 Aug 2.
PMID: 28770420DERIVEDFernandez O, Giovannoni G, Fox RJ, Gold R, Phillips JT, Potts J, Okwuokenye M, Marantz JL. Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM. Clin Ther. 2017 Aug;39(8):1671-1679. doi: 10.1016/j.clinthera.2017.06.012. Epub 2017 Jul 25.
PMID: 28751099DERIVEDFox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.
PMID: 27733070DERIVEDGold R, Giovannoni G, Phillips JT, Fox RJ, Zhang A, Marantz JL. Sustained Effect of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Interim Results From an Extension of the DEFINE and CONFIRM Studies. Neurol Ther. 2016 Jun;5(1):45-57. doi: 10.1007/s40120-016-0042-8. Epub 2016 Mar 1.
PMID: 26932146DERIVEDGiovannoni G, Gold R, Fox RJ, Kappos L, Kita M, Yang M, Sarda SP, Zhang R, Viglietta V, Havrdova E. Relapses Requiring Intravenous Steroid Use and Multiple-Sclerosis-related Hospitalizations: Integrated Analysis of the Delayed-release Dimethyl Fumarate Phase III Studies. Clin Ther. 2015 Nov 1;37(11):2543-51. doi: 10.1016/j.clinthera.2015.09.011. Epub 2015 Oct 31.
PMID: 26526385DERIVEDNakamura K, Brown RA, Narayanan S, Collins DL, Arnold DL; Alzheimer's Disease Neuroimaging Initiative. Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations. Neuroimage. 2015 Sep;118:126-32. doi: 10.1016/j.neuroimage.2015.05.077. Epub 2015 Jun 3.
PMID: 26049148DERIVEDKita M, Fox RJ, Gold R, Giovannoni G, Phillips JT, Sarda SP, Kong J, Viglietta V, Sheikh SI, Okwuokenye M, Kappos L. Effects of delayed-release dimethyl fumarate (DMF) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: an integrated analysis of the phase 3 DEFINE and CONFIRM studies. Clin Ther. 2014 Dec 1;36(12):1958-1971. doi: 10.1016/j.clinthera.2014.08.013. Epub 2014 Oct 12.
PMID: 25315404DERIVEDFox RJ, Kita M, Cohan SL, Henson LJ, Zambrano J, Scannevin RH, O'Gorman J, Novas M, Dawson KT, Phillips JT. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2014 Feb;30(2):251-62. doi: 10.1185/03007995.2013.849236. Epub 2013 Oct 22.
PMID: 24131282DERIVEDGold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1098-107. doi: 10.1056/NEJMoa1114287.
PMID: 22992073DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Biogen Idec Study Medical Director
- Organization
- Biogen Idec
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 8, 2007
First Posted
January 11, 2007
Study Start
January 1, 2007
Primary Completion
February 1, 2011
Study Completion
February 1, 2011
Last Updated
January 26, 2015
Results First Posted
June 2, 2014
Record last verified: 2015-01